Sodium butyrate ameliorates muscle atrophy in type 2 diabetes-related sarcopenia via the PI3K/Akt/FoxO1 pathway

Type 2 diabetes-related sarcopenia is progressively acknowledged as a complication of type 2 diabetes that contributes to disability and diminished quality of life. Growing evidence indicates that the short-chain fatty acids (SCFAs) are essential regulators of metabolic homeostasis. A link between butyrate and type 2 diabetes has recently been established, but its connection with muscle wasting remains unknown.

Eight-week-old db/db mice, representing an animal model for type 2 diabetes-related sarcopenia, received sodium butyrate (150 mM) for 12 weeks. Gastrocnemius muscles were harvested for analysis by H&E staining, Western blot, and RT-qPCR analyses. In parallel, palmitic acid-induced atrophy in C2C12 myotubes was employed to evaluate the PI3K/Akt/FoxO1 pathway and its phosphorylated proteins using Western blot. The role of this pathway was further verified through application of the Akt inhibitor MK2206.

In this study, we noted that eight-week-old db/db mice model type 2 diabetes-related sarcopenia, exhibiting reduced muscle strength and exercise endurance. Palmitate-induced C2C12 myotube atrophy, a validated in vitro model, resulted in diminished myotube diameter and upregulated expression of atrophy-related proteins. Both animal and cell-based studies show that sodium butyrate boosts muscle strength and fiber size. It operates through the activation of the PI3K/Akt/FoxO1 pathway, which in turn lowers the levels of proteins linked to muscle wasting.

Research indicates that sodium butyrate attenuates type 2 diabetes-related sarcopenia via the activation of PI3K/Akt/FoxO1 signaling. Consequently, this short-chain fatty acid may serve as a viable intervention for patients suffering from sarcopenia in the context of type 2 diabetes.